Antiepileptic drug distribution in cerebral cortex, ammon's horn, and amygdala in man

Significant correlations in the concentrations of phenobarbital, phenytoin, and carbamazepine in the brain, plasma, and cerebrospinal fluid were found in 12 surgically treated epileptic patients. These findings confirm the clinical reliability of monitoring anticonvulsant drug plasma levels as part of the routine management of epilepsy. Phenobarbital, phenytoin, and carbamazepine are uniformly distributed in the gray and white matter in different brain areas (except for a higher concentration of phenobarbital in the rhinencephalic structures in comparison with the corresponding temporal neocortex) and in normal and scar tissue. In these 12 patients, all of whom were medically resistant, molar cortex concentration of phenobarbital and phenytoin was at "therapeutic" levels or even higher. These data suggest that in therapy-resistant patients, despite cerebral drug concentrations of the same therapeutic level as, or higher than, those present in medically controlled patients, anticonvulsant drugs are pharmacologically ineffective.